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Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

Lai Y, Zhong W, Yu T, Xia ZS, Li JY, Ouyang H, Shan TD, Yang HS, Chen QK - PLoS ONE (2015)

Bottom Line: The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.COX expression was significantly down-regulated in aspirin induced SII (P < 0.05).In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.

Methods: BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.

Results: COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).

Conclusion: Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

No MeSH data available.


Related in: MedlinePlus

Body weights and histological changes of small intestines in mice.(A) The body weights of mice in the four groups were shown. The bars indicated the body weights of mice measured by gram (n = 6, *P < 0.05 when compared with Con-Reb and Con-Sal groups). (B) Histological changes of mice in the four groups were shown. In the SII-Reb and SII-Sal groups, the small intestine showed acute transmural injuries with villi atrophy, inflammatory cell infiltration, cell swelling, epithelial cell necrosis, and dilation of sub-epithelial space at day 5. The small-intestine enteritis of the SII-Reb mice after rebamipide administration was milder than that of the SII-Sal mice at day 10 (Bar indicates 50 μm).
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pone.0132031.g001: Body weights and histological changes of small intestines in mice.(A) The body weights of mice in the four groups were shown. The bars indicated the body weights of mice measured by gram (n = 6, *P < 0.05 when compared with Con-Reb and Con-Sal groups). (B) Histological changes of mice in the four groups were shown. In the SII-Reb and SII-Sal groups, the small intestine showed acute transmural injuries with villi atrophy, inflammatory cell infiltration, cell swelling, epithelial cell necrosis, and dilation of sub-epithelial space at day 5. The small-intestine enteritis of the SII-Reb mice after rebamipide administration was milder than that of the SII-Sal mice at day 10 (Bar indicates 50 μm).

Mentions: The total body weights of mice in group SII-Reb, group SII-Sal, group Con-Reb, and group Con-Sal were observed during the 10-day period (Fig 1A). The total body weights of mice in SII-Reb and SII-Sal group showed a significant decrease from day 0 to day 5. However, the body weights of SII-Reb mice increased and there were significant differences when compared with the SII-Sal mice at day 10 (P < 0.05). There were no unexpected deaths throughout the observation period. These results demonstrated that rebamipide administration after aspirin-induced SII could significantly ameliorate the nutritional status of mice.


Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.

Lai Y, Zhong W, Yu T, Xia ZS, Li JY, Ouyang H, Shan TD, Yang HS, Chen QK - PLoS ONE (2015)

Body weights and histological changes of small intestines in mice.(A) The body weights of mice in the four groups were shown. The bars indicated the body weights of mice measured by gram (n = 6, *P < 0.05 when compared with Con-Reb and Con-Sal groups). (B) Histological changes of mice in the four groups were shown. In the SII-Reb and SII-Sal groups, the small intestine showed acute transmural injuries with villi atrophy, inflammatory cell infiltration, cell swelling, epithelial cell necrosis, and dilation of sub-epithelial space at day 5. The small-intestine enteritis of the SII-Reb mice after rebamipide administration was milder than that of the SII-Sal mice at day 10 (Bar indicates 50 μm).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489841&req=5

pone.0132031.g001: Body weights and histological changes of small intestines in mice.(A) The body weights of mice in the four groups were shown. The bars indicated the body weights of mice measured by gram (n = 6, *P < 0.05 when compared with Con-Reb and Con-Sal groups). (B) Histological changes of mice in the four groups were shown. In the SII-Reb and SII-Sal groups, the small intestine showed acute transmural injuries with villi atrophy, inflammatory cell infiltration, cell swelling, epithelial cell necrosis, and dilation of sub-epithelial space at day 5. The small-intestine enteritis of the SII-Reb mice after rebamipide administration was milder than that of the SII-Sal mice at day 10 (Bar indicates 50 μm).
Mentions: The total body weights of mice in group SII-Reb, group SII-Sal, group Con-Reb, and group Con-Sal were observed during the 10-day period (Fig 1A). The total body weights of mice in SII-Reb and SII-Sal group showed a significant decrease from day 0 to day 5. However, the body weights of SII-Reb mice increased and there were significant differences when compared with the SII-Sal mice at day 10 (P < 0.05). There were no unexpected deaths throughout the observation period. These results demonstrated that rebamipide administration after aspirin-induced SII could significantly ameliorate the nutritional status of mice.

Bottom Line: The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.COX expression was significantly down-regulated in aspirin induced SII (P < 0.05).In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.

ABSTRACT

Background: The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.

Methods: BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.

Results: COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).

Conclusion: Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.

No MeSH data available.


Related in: MedlinePlus